Nitroreductase (NTR)-Triggered Degradable Polymeric Sulfur Dioxide (SO <sub>2</sub> ) Prodrug
A nitroreductase (NTR)-responsive sulfur dioxide (SO<sub>2</sub>)-releasing polyurethane-based polyprodrug system is developed to execute enzyme-responsive gas therapy under hypoxic conditions. The self-assembled characteristics of the amphiphilic polyurethanes are thoroughly investigated, and their enzyme-triggered degradation is elucidated by size exclusion chromatography (SEC), hydrodynamic diameter (<i>D</i><sub>h</sub>) measurement, and microscopic study. Additionally, NTR and SO<sub>2</sub>-responsive small molecular and polymeric fluorescent probes are synthesized, and the respective responsiveness is studied by <sup>1</sup>H NMR and fluorescence spectroscopy. Hypoxia-activated anticancer drug tirapazamine (TPZ) is encapsulated into the polymeric nanoaggregates, and 63% drug release is observed at pH 6.0 in the presence of NTR. Anticancer activity of the polyprodrug (SO<sub>2</sub> as a cytotoxic agent) and TPZ-loaded polymeric nanoaggregate (SO<sub>2</sub> and TPZ as cytotoxic agents) is demonstrated with cobalt chloride (CoCl<sub>2</sub>, hypoxia mimetic mediator). Overall, the present work reveals the impact of the NTR-responsive degradable polyprodrug as an anticancer therapeutic and gives a new perspective on enzyme-responsive gas therapy.
Authors
- Desoshree Ghosh (ORCID: https://orcid.org/0009-0006-4943-5058)
- Priyadarsi De (ORCID: https://orcid.org/0000-0001-5486-3395)
- Arunava Seth (ORCID: https://orcid.org/0000-0001-8544-3457)
- Sagar Bag (ORCID: https://orcid.org/0000-0002-8094-193X)
Institutions
- Indian Institute of Science Education and Research Kolkata (IN)
- Institute of Molecular Functional Materials (CN)
Publication Details
- Journal
- Biomacromolecules
- Published
- 2025-10-03
- DOI
- https://doi.org/10.1021/acs.biomac.5c01047
- Citations
- 1
- Primary Topic
- Nanoplatforms for cancer theranostics
- Type
- article
- Field-Weighted Citation Impact
- 0.67